10alpha-steroids and process for their manufacture



United States Patent ration of Delaware No Drawing. Filed July 9, 1963, Ser. No. 293,888

Claims priority application Switzerland July 10 1962, 8,298/62; Ai 17, 1962, 9,845/623Mar. is, 1963,

10 Claims. (Cl. 260-3973) The present invention relates to A and A -3-oxosteroids having the unnatural rut-configuration of the angular methyl group in position; and to a new process for the manufacture thereof. Said compounds are designated herein briefly as A*- and A -3-oxo-l0a-steroids. They are obtained from certain irradiation products of A -3oxo-steroiddienes that contain the natural ,B-configuration of the angular methyl group on carbon atom 10.

The products of the present process are therapeutically active compounds or intermediates suitable for the manufacture thereof. Thus, in particular, the compounds of the IOu-andrOst-a-ne and IOa-pregnane series display valuable pharmacological properties, for example an antiandrogenic and ovulation inhibiting action respectively. Of particular value is Illa-testosterone, its esters and its derivatives substituted in position 17 a by saturated or unsaturated hydrocarbon radicals, as well as the corresponding derivatives which are dehydrogenated in 1,2-position. The compounds of the IOu-pregnane series exhibit particularly also a igestagenic activity.

The few A -3-ox-o-1Ou-steroids known have hitherto been accessible only by way of complicated total syntheses. It has now been found that from the A -2-oxo-1:5fi-cyclo- Ida-steroids (which are obtained in good yields by irradiating A -3-oxo-steroid dienes, as described in Belgian Patent No. 564,254, patented July 25, 1958, to Ciba Socit Anonyme (cf. erg. ketone B of that patent) A -3-oxo-l0a-steroids can be obtained in a simple manner. According to the present processfor the manufacture of these compounds the A -double bond in A -2-oxo-lz5f3- cyclo-lou-steroids is hydrogenated, the resulting saturated ketone is treated with a strong acid in the presence or absence of an acylating agent, the possibly resulting enol acylate is oxidized with selenious acid or a derivative thereof, or hydrolyzed with an aqueous acid, A -2-oxoor 2-oxo-5a-acyloxy-w t-steroids which are possibly obtained are reacted with lead tetraacylate in the presence of [glacial acetic acid and a strong acid, the resulting A -2- acyloxy-3-oxo-10a-steroid is heated with zinc in a solvent, if desired the A -3-oxo-l0a-steroids obtained are converted into A -3-oxo-10a-steroids by irradiation and/or, if desired, a possibly formed ester is hydrolyzed in known manner before or after the introduction of a A -double bond, and the resulting hydroxysteroid is dehydrogenated in known manner.

The reactions of the present process are illustrated, for example, in the following scheme of partial formulae:

T-he A -d0uble bond is saturated, for example, by catalytic hydrogenation, preferably in an alcoholic, for instance ethanolic, solution and in the presence of a noble metal catalyst, for example a palladium+carbon catalyst.

The strong acids used in the present process are for example anhydrous mineral acids or sulfonic acids, such as sulfuric, hydrobromic, para-toluenesulfonic or methanesulfionic acid. Particularly suitable are also Lewis acids, such as zinc chloride, tin tetrachloride, aluminum chloride and more especially boron trifluoride inthe form of its ether complex.

If the splitting of the C -C bond is carried out in the presence of acylating agents, enol acylates, viz A -2:5adiacyloxy l0a-steroids, are obtained, while in the absence of acylating agents, for example in solution of a lower aliphatic carboxylic acid such as formic, acetic or propionic acid,A -2-oxo-l0u-steroids are obtained. It is advantageous to employ as acylating agents anhydrides and halides of lower aliphatic carboxylic acids, for example of acetic, propionic, butyric, pivalic, chloracetic, trichloracetic or trifluoraceti'c acid. These agents are advantageously also used as solvents. The splitting is preferably carried out at temperatures ranging from to 0 C.

Fort-he oxidation of the enol acylates, selenious acid or a derivative thereof, such, for example, as selenium dioxide or an ester of selenious acid, is used in a suitable solvent that is stable towards the oxidant, for example in a lower aliphatic carboxylic acid such as acetic or propionic acid, or in a cyclic ether, more especially in dioxane. The oxidation of the invention gives A -2-acyl oXy-3-oxo-10a-steriods directly in one step with introduction of an oxygen function in position 3 and simultaneous elimination of the Sa-a-cyloxy group.

The identical compounds are obtained when the 2- enol acylates obtained in the first reaction stage of the present process (acylolytic splitting of the three-membered ring) are hydrolyzed with aqueous acids and the resulting 2foxo compounds are subjected to the action of a lead tetraacylate, for example lead tetraacetate, in a suitable solvent. The acids used are preferably mixtures of lower aliphatic carboxylic acids such as formic, acetic and propionic acid, with water in the presence of a small tageously performed in lower aliphatic carboxylic acids,

for example in acetic, propionic or trifluoracetic acid, in the presence of the above-mentioned strong acids.

Treatment of the A -2-oxo-10a-steroids obtained by the present process with a lead tetraacylate, such as lead tetraacetate, also gives the above-mentioned A -2g-acyloxy-3- oxo-lOa-steroids. compounds, for instance with alkaline agents such as bicarbonates of alkali metals or with acids such as for instance diluted mineral'acids, e;g; hydrochloric acid, there are obtained the corresponding free hydroxy-compounds, namely A -2-hydroxy-3-oxo-1Ova-steroids.

The reduction with zinc, which brings about elimination of the 2-acyloxy group and leads to the final products of the present process-the A -3-oxo-lOa-steroidsis advantageouslycarried out in a solvent. Suitable .for this purpose are, for example, lower aliphatic alcohols, such as methanol, ethanol, propanoLbutanol or the like; "also,

for example, anhydrides of aliphatic carboxylic acids, such,

as acetic anhydride, and more especially aliphatic carboxylic acids such as acetic, propionic or other acids. The reduction according to the invention is preferably carried out at the boiling temperature of the solvent used.

By irradiating the A -3-ox0-10a-steroids obtained by the present process in an inert solvent, such as lower aliphatic alcohols, for instance methanol, ethanol, propanol, buta- By s-aponification of the last-named,

n01, especially tertiary butanol, or in an ether, such as di- 7 oxane, or in an aliphatic, cycloaliphatic or aromatichydrocarbon,'for instance in cyclohexane or benzene, with ultraviolet light, there may be obtained from the reaction mixture for instance by chromatography on neutral aluminium oxide, the corresponding isomeric A -3-oxo-10u-steroids. These steroids are suitable starting compounds for the introduction of subs-tituents in position 6 of the nucleus. For the aforementioned irradiation there are preferably used high pressure mercury arc lamps.

The A -3-oxo-10a-steroids can also be dehydrogenated in 1,2-position in a manner known per se for instance with the aid of quinones, such as dicyanodichlorobenzoquinone. As solvents there are used liquids which are resistant to the action of the oxidation agent, such as for instance, hydrocarbons, for instance benzene, tertiary lower aliphatic alcohols, such as tertiary butyl alcohol, tertiary amyl alcohol or ether and, preferably, dioxane. The dehydrogenation may also be carried out in a manner known per se with the aid of selenium dioxide.

If it is desired to hydrolyze acyloxy groups in the A or A -3-oxo-10a-steroids obtained, for example a 17,8- acyloxy group in an androstane or a ZO-acyloxy groupin a p-regnane, this is advantageously'performed in known manner by treatment with bases, for example with alkali metal or alkaline earth metal bicarbonates, carbonates or hydroxides, for example with sodium, potassium or lithium bicarbonate, carbonate or hydroxide, or with calcium or barium carbonate or hydroxide.

The dehydrogenation of hydroxyl groups (for ex-' ample of a hydroxyl group in position 17, 11 or 20) is likewise performed in known'manner, preferably however by oxidation with a derivative of hexavalent chromium, for example with chromium trioxi'de in pyridine or in acetone+sulfiuric acid, with potassium bichromate or the like. Likewise suitable are derivatives of the hypohalous acids, for example tertiary butyl hypochlorite; N-bromosuccinimide and the like. When the product obtained by the present process is a 17-oxoandr-ostane, for example A -3zl7-dioxo-10a-androstene, it is possible to introduceinto itafter the A -3-oxo-groupings has been selectively protectedim knownmanner, for example by reaction with a Gri-gnard compound or an organo-metal compound of the typeof lithium acetylide or methyl lithium, a 1711-. alkyl, Hot-alkenyl or a 17a-alkinyl residue. The sub,

sequent removal of the protective group then results in a 17-su'bstituted A -3-oxo-l0a-androstene.

Statring materials suitable for use in thepresent process are A -2-ox0-1:5/3-cyclo-lowsteroids, belonging eQg. to

the androstane, pregnane, cholane, cholestane, 'spirostaneand card-anolide S61'l6S,WhlCh may contain in the ring system, more especially in one 10]: several of the positions 7, 8,9, 11, 12, 14, 15,16, 17, 20, 21 and in the. side-chain, further substituents such as lower :alkyl, for example methyl, groups, halogen atoms, free; or functionally oonverted (that'is to say esterifiedon etheriiiedy hydroxyl groups and/or carbalkoxy groups; Particularly important starting materials are .the representatives of the A 1 2-.ox-0-l Sfi-cyclo-lOa-androstenes' and -10a-pregnenes, forexample A -2-0xo-1 :5 /3-cyclo-17fl hydroxy-l0a-androstenei and its esters,- A -2-oxo-1:5,8-cyclo-17/3-acyl0xyrl7a-alkyl-, for example stenes,

The aforementioned starting materials are advantageously prepared fronr:the corresponding :A -3-oxosteroids as described in the afore-mentioned Belgian Pat,- ent No. 564,254, by irradiation with ultravioletlight followed by separation of the resulting reaction mixture of 1 phenols and ketones. This'can be achievedfor instance by,.chromatography on aluminum oxide and elutriation with benzene. The compounds-which can be used as the starting steroidsin thetpresent invention can be identified on the basis of their characteristic ultraviolet ab sorption spectrumwhichl has a Amax, at about 238 my and an end absorption atabout 207 in (cf. for instance I ketone B in the aforementioned iBelgian.-Patent No.

All the other ketonic constituents show their longest ultraviolet absorption band at wave lengths over- The present process yieldsibyneaction of. the afore mentioned startingmaterials A 1, A -for A F -3-oxo-l0asteroids and their: esters, more especially such of the loa -androstane and lOa-pregnane series.

Of special importance are,- for example compounds of the formulae and which contain in the 4-, 5- or 1:4-position a double bond and wherein R represents a hydroxy or 'acyloxy group, R2 a hydrogenatom or a lower alkyl, alkenyl oralkinyl group, R andsR together alsoan 0x0 group, R two hydrogenatoms, an oxo group or an uor SI-positioned hydroxy group and a hydrogen atom, R, a hydrogen atom or a methyl group, R a hydrogen atom, a hydroxy or acyloxy groupand R an 0x0 group or a hydroxy or acyloxy .group anda hydrogen atom; Special mention deserve the following compounds:

1 Ou-pregnene,

1,2-position,

A -3-oxo-17fi-hydroxy-lOa-androstene and its esters, A -3:17-dioxo-1Oa-androstene, A -3-oxo-17a-alkyl-, 17aalkenyland 17a-alkinyl-l7/3-hydroxy-Illa-androstene and their esters, such, for example as A -3-oxo-l7a-methyl-, 17u-ethyl-, -17a-vinyland 17a-ethinyl-17fl-hydroxy-10aandrostene and their esters; also the A -3-oxo-20-hydroxyu-pregnenes and their esters, A -3:20-dioxo-10a-pregnene and its substitution products, among others A 3: ll :20-trioxo-l0a-pregnene, A -3 :20dioxo-l6a-methyl- A -3 20-dioxo-17u-acyloxy-10a-pregnenes and the corresponding compounds dehydrogenated in the such as l-dehydro-wot-testosterone, l-dehydro 17a methyl-10a-testosterone and l-dehydro-lOaprogesterone, but also A -3-0X01Ouandrostenes and -pregnenes, such as A -3-oxo-17;8-hydroxy-1Ont-androstene and its esters and A -3,20-dioxo-10a-pregnene.

The invention further includes the 2-oxo-5a-acyloxy- Not-steroids, more especially the 2-OXO-5a-21CY1OXY-10otandrostanes and -pregnanes for example such of the formulae in which R to R have the meanings given above. There may-be mentioned specifically: 2-oxo-5a-acy1oxy-17 8-hydroxy-lOa-androstane and its esters, 2-oxo-5m17B-diacyl- OXY-l'loc-ZllkYl, for example -17a-methy1- and 17u-ethyl- 10a-androstanes, 2-oxo-5a-acyloxy-2O-hydroxy-IDOL-pregnanes and their esters, and 2-0-X0-5a1l1oc220- and 5a:ll6:ZO-triacyloxy-lOa-pregnanes. Mention may also be made of the corresponding A -2OX0-10u-St6I0idS, more especially the A -2-oxo-10a-androstenes and -pregnenes, for example A -2-oxo-17/8-hydroxy-1Out-androstene or A 2-oxo-17,8-hydroxy-17a-methyl-10at-androstene and their esters.

The invention includes alsothe new A -2g-acyloxy-3- oxo 10oz androstenes and -10a-pregnenes and the free hydroxy compounds obtainable therefrom, for example such of the formulae CH3 CH3 R1 sure or buffers.

and

wherein R7 represents a hydroxy or acyloxy group and R to R have the meanings given above. Specific compounds are, for example, A -2izl7fl-dihydroxy-3-oxo-l0aandrostene and its esters, Ai-Zg: 17/8-dihydroxy-3-oxo-17amethyland 17a-ethyl-10a-androstene and their esters, A -2:11a:20- and A -2z11,8:20-trihydroxy-3-oxo-10apregnene and their esters.

The acid radicals in the above-mentioned esters are especially those of aliphatic, cycloaliphatic, araliphatic, heterocy-clic or aromatic carboxylic acids, preferably of such as contain 1-15 carbon atoms, for example formates, acetates, propionates, butyrates, trimethylacetates, oenanthates, caproates, decanoates, cyclopenty-lproprionates, valerates, benzoates, furoates, hexahydrobenzoates, phenylpropionates, trifluoracetates, ethylcarbonates, methylcarbonates or the like.

The conversion of the A or A -3-oxo-10a-compounds obtained as products of the present process and belonging for example to the spirostane or cholestane series, into the corresponding biologically active representatives of the androstane and pregnane series can be carried out in known manner egg. by acylolysis and/ or by oxidation.

The new pharmacologically active compounds can be used for the manufacture of pharmaceutical preparations.

More particularly the preparations of the present invention are characterized by the content of one of the new .A*- and A -3-oXo-10oc-steroids, especially of the androstane and pregnane series, together with a solid or liquid medicinal excipient. The preparations are made by as 'suchlanown methods, forexample, with the use of pharmaceutical organic or inorganic excipients, suitable for parenteral, enteral and particularly oral, or also topic administration. Suitable excipients are substances: that do not react with the new compounds such, as for example, water, vegetable oils, benzyl alcohols, polyethyllactose, starch, magnesium stearate,

talc, white petroleum jelly, cholesterol or other medicinal excipients. More especially, preparations are made which are suitable for parenteral administration, preferably solution, above all oily or aqueous solutions: furthermore suspensions, emulsions or implants; for enteral administration there are also made tablets or dragees, and for local administration also ointments or creams. If desired the preparations may be sterilized or they may contain assistants such as preserving, stabilizing, wetting or emulsifying agents, salts for regulating the osmotic pres- They may also contain other therapeutically active compounds. They are prepared in the known manner. The content of the active substance in these preparations, such as of a tablet, is preferably 0.1-

.20 mg. of 0.0350%, especially 0.1 to 10% by weight.

Said pharmaceutical preparations can be used in human or veterinary medicine.

The invention is illustrated more fully in the following examples. The optical rotation is measured in each case in chloroform. The melting points are uncorrected.

Example 1 A mixture of 11 g. of A -2-oxo-1:5fi-cyclo-17B-acetoxy- IDOL-androstene, 200 cc. of ethanol and 2 g. of palladium carbon catalyst of 5% strength is hydrogenated. When 1 mol of hydrogen has been absorbed, the catalyst is filtered off and the filtrate is evaporated under vacuum.

poured into ice water and extracted with ether. crude product is filtered through neutral alumina (activity.

The starting material used. is the ketone B described. in the afore-mentioned Belgian Patent No. 564,254,-

[a]D=14s (c.=0.70), UV-spectrum unax.= 1 g e=3.34).

Example 2 A solution of g. of 2-oxo-1:Sfl-cycld-IZB-acetoxy- 10a-andr0stane in 400 cc. of acetic anhydride .is cooled to 60 C. 12.5 .cc. of boron trifluoride ethereate are then dropped in and the mixture is kept for 5% hours at -50 to .60 C. The colorless solution is then The III) and gives on recrystallization from acetone-i-hexane 11.5 g. of A -2:5a:17/3-triacetoxy-1()u-androstene melting at 167-168 C. Optical rotation [oc] =+4-3 (c.=0.69). Infrared spectrum in potassium bromide: x =1764, 1730, 1690 cm.

When .2-oxo-1:5 3-cyclo-20p-acetoxy-10a-pregnene, is

treated in identical manner, it yields N-ZzSmZOB-triacetoxy-lW-pregnene. Infrared spectrum: A ==-1765, 1730, 1690 cmr Example 3 A solution of 1.940 g. of A -2:5a:l7 3-triacetoxy-l0ot- :androstene in cc. of glacial acetic acid is mixedwith 10 cc. of water and 70 drops of concentrated sulfuric acid. The solution is left toitself for hours at'room temperature, then poured into /2 liter. of water and extracted with 2 liters of ether.

The organic phase is washed with water, mixed with 200 cc. of benzene, and

evaporated under vacuum. The residue is further acetylated overnight at room temperature in 50 cc. of a 1:1- mixture of acetic anhydride and pyridine. The solvent 'is thenevaporated under vacuum, the residue filtered through neutral alumina (activity III) and the crude prod-f uct is crystallized from acetone+hexane, to yield 1.426 g; of 2-oxo-5a:17,3-diacetoxy-10u-androstane' melting at: 187-188" C. Optical rotation [u] =+40 (c.=0.50). Infrared spectrum in Nujol: =1733 (shoulder), 1724, 1257, 1246 cm.-

When 2.5 g. of A -2:5a:20 8-triacetoxy-ltlot-pregnene are hydrolyzed under the conditions as described above, there are obtained 1.80 g. of pure 2-oxo-5az20fi-diacetoxy- IOu-pregnane.

- Example 4 (A) A solution of 200 mg. of'A -2z5azl7B-triacetoxy- IOa-andrnstene in 10 cc. of. dioxane is mixed .with 200 mg. of selenium dioxide and the whole is refluxed for 20-h0urs, then cooled, filtered, the residue is rinsed with' benzene, and'the filtrates are evaporatedunder vacuum. Chromatography of the crude product on neutral alumina (activity III) with a 4:1-mixture of petroleum :ether and-benzene furnishes mg. of unreacted starting material, and elution with benzene yields 28 mgof A 25:l7fi-diacetoxy-3-0xo-IOa-androstene which melts at 225 C. after four recrystallizations from acetone+hex ane and sublimation in a high vacuum at 185 C. Optical rotation, [u] =-191 (c.=0.86). Ultraviolet spectrum: h =244 m,u. (e=15,400'). Infrared spectrum is chloroform: )Nm x =1725, 1735, 1682, 1625, 1255 cmr (B) 780 mg. of 2-oxo-5a:17/3-diacetoxy-IOm-andmstane in 50 cc. 'of glacial acetic acidare stirred at room temperature. under nitrogen with 1.020 g. of lead tetraacetate (containing about; 10% of glacial acetic acid) and with 1.5 cc. of boron trifluorideetherate. After 1% hours reaction the batch is poured over ice,.extracted with iether andthe etherealextract is washedwit-h sodium bicarbonate solution and water. The resulting .oil (850 mg.) is chromatographed on 50 times its own weight of neutral alumina (activity III). A -1::l,-mixture of petroleum ether-l-benzene elutes' 282 mg. of unreacted starting material. Thereafterthe same solvent-mixture and benzene elute 329 mg. of crystals which melt at 225 C. after recrystallization from acetone-l-hexane and sublimation in a high vacuum. 1 According to the mixed melting point test, infrared andultraviolet spectra this productis identicalwith the compound obtained under (A) above.

When; 1.2 g. of. 2-oxo-5a:ZOB-diacetoxy-IOa-pregnane are treated in an identical manner and thenchromatographically purified, thereare obtained 385 mg. of A 25:20 3-diacetoxya3oxo-loot-pregnene.

Example 5 1 Asolution of 185 mg. of A 2:17,8-diacetoxy-3-oxo-' l0a-androstene in 10cc. of glacialacetic acid is'mixed, with 200 mg. of zinc dust and heatedto=the boil. In

the course :of 2 hours. another 200' mg. of zinc dustare stirred-in portionwise, ;and the .mixture ;is cooled and evaporated to dryness under vacuum. Chromatography on neutral alumina (activity 11)! and 'elution with hexane+benzene (3:2) and with benzene furnishes mg. of crystals which after two recrystallizations from methylene chloride+hexane and sublimation in a high vacuum at C. furnish 10a-testosterone-NIB-acetate melting at 146 C. Optical rotation, [oz] =222 (c.=0.6 7). Ultraviolet spectrum: M :245 m (e=l5,980)- Infrared spectrum in chloroform: h =17.20,'1660,- 16 25, 1255 'cmri fi The subsequent hydrolysis of the above compounds with aqueous-methanolic potassium hydroxide? solution under nitrogen for l6 hours at 25 C; furnishes in a substantially quantitative yield free wot-testosterone which melts at '146' C. after recrystallization from. ether+hexane followed by sublimation in a high vacuum.

Optical rotation [a] .=2O8 (c.=0.73).

An analogous;reduction and subsequent hydrolysis of' 200 mg. of A -2:20/8-diacet0xy-3-oxo-IOa-pregnene given rise to A 43-oxo-20/3-hydroxy-10a-pregnene which, on oxidation with chromium'trioxide in pyridine at 25 C. for 16 hours, furnishes 105 mg. of l0a-progesterone.;-.

Example 6 130-mg..of 3 oxo 17B acetoxy 1:5 cyclo-10w.

androstane are mixed with 3 .cc. ofa solution of 0.1 g. of concentrated sulfuric acid in 10 cc. of glacial-acetic acid and the mixture is heated for 2 hours to 95 C. The

normally worked .up reaction mixture is dissolved in ben- -zene and filtered throughil g. of neutralalumina (activ-.

Afterrecrystallization i from. acetone-khexane, the 111 ;mg..of A t-2-oxo-17 8-acetoxy-l 0a-androstene ob- I ity II) tained melts at 181182 C. Opticalrotation [a] 55 (c.=0.98).. Infrared. spectrum'qin chloroform: 1725,1710, 124.0 cmr Tetranitromethane' test: yellow.

Example 7 200 mg. of O acetyl -l0ot-testosterone (cf. Example 5) in 30 cc. of dioxane are .boiled and stirred for 8 hours with 500mgaof: dichloro-dicyan-benzoquinone. When the solution has cooled, iit'is diluted with Tether, filtered and evaporated. The crudepr'oduct obtained is dissolved in methylene chloride, the solution filtered through the ten-fold quantity of alumina (activity 111), the fractions obtained are evaporated under vacuum, the residues combined and dissolved in 20 cc. of methanol and the S0111- tion boiled for '10 minutes with active carbon. The

reaction mixture is freed from the active carbon and then concentrated to obtain 100 mg. of O-acetyl-l-dehy- CII'O-IOa-tCStOStCIOIIB which after having been recrystallized twice from a mixture of acetone and petroleum ether have a constant melting point at 127 C. [a] -78. (c. 099). The IR spectrum of the compound shows bands, inter alia at 1725, 1664, 1625, 1607 and 1260 cmr x =247 III/L (6=15,900).

45 mg. of the compound so obtained yield, when boiled for 1 hour in 10 cc. of 5% methanolic potassium hydroxide solution and worked up, 44 mg. of crystals. On filtration through neutral alumina (activity III) and two crystallizations from acetone+petroleum ether, the pure l-dehydro-IDOL-testosterone of melting point 95-97 C. [a] =70 (c.=0.68) is obtained. The IR spectrum shows bands inter alia at 3620, 1660, 1620 and 1605 ccf A =247 Il'1,u. (e=13,250).

By treating in an analogous manner 230 mg. of 100:- progesterone in 50 cc. of dioxane with 700 mg. of dichloro-dicyan-benzoquinone, 205 mg. of crude l-dehydro-u-progesterone are obtained. M :247 m (6: 12,800). The IR spectrum of the crude compound shows bands inter alia at 1704, 1663, 1625 and 1605 cm.-

Example 8 A solution of 950 mg. of IOtx-tfiStOStGIOIlC in 500 cc. of tertiary butanol is irradiated for 72 hours with a high pressure burner Q81 (made by Quarzlampen G.m.b.H., Hanan, Germany), at room temperature in a central water-cooled quartz jacket. The solvent is evaporated in vacuo and the oily residue chromatographed over 24 g. of neutral alumina (activity III). Eluation with benzene yields 197 mg. of crystalline A -3-0X0I7B-hYdI'OXY-1Oocandrostene. Melting point after two recrystallizations from acetone+petroleum ether: 173174 C. [a] -119 C. (c.=0.66). IR spectrum (CHCl 11 3640, 1712, 1668 cm.- UV spectrum (ethanol): :213, 293 m (5:2040, 170).

With mixtures of benzene and ether (9:1), 213 mg. of unchanged starting material are isolated.

What is claimed is:

1. A compound of the formula wherein R is a member selected from the group consisting of hydroxy and acyloxy, said acyloxy being derived from a carboxylic acid having 1 to 15 carbon atoms, and R is a member selected from the group consisting of hydrogen, lower alkyl, lower alkenyl and lower alkinyl, and R and R taken together, is 0x0.

2. 2oxo-5a,17,8-diacetoxy-10m-androstane.

3. A compound of the formula CH3 CH Oacyl wherein R is a member selected from the group consisting of two hydrogen atoms, the 0X0 group, a-hydroxy and CH3 R1 wherein R is a member selected from the group consist ing of hydroxy and acyloxy, said acyloxy being derived from a carboxylic acid having 1 to 15 carbon atoms, R is a member selected from the group consisting of hydrogen, lower alkyl, lower alkenyl and lower alkinyl, and R and R taken together, is 0x0.

7. A -2-oxo-17B-acetoxy-IOa-androstene.

8. Process for the manufacture of A -3-oxo-10a-steroids, wherein a A -2-oxo-1,5fi-cyclo-10a-steroid selected from the group consisting of those of the androstane, pregnane, cholane, cholestane, spirostane and cardanolide series is hydrogenated with hydrogen catalytically activated with a noble metal catalyst, the 2-oxo-1,5B-cyclo- IOa-steroid obtained is treated with a member selected from the group consisting of a strong acid selected from the group consisting of an anhydrous mineral acid, a lower aliphatic sulfonic acid, a monocyclic aromatic sulfonic acid and a Lewis acid; and mixtures of such acids with a member selected from the group consisting of an anhydride and a halide of a lower aliphatic carboxylic acid selected from the group consisting of an anhydride and a halide. of a lower aliphatic carboxylic acid, the enol acylate obtained is treated with a member selected from the group consisting of selenious acid, a selenious acid ester, selenium dioxide and an aqueous acid, a resulting 2-oxo-l0ot-steroid is reacted with a lead tetraacylate and the A -2-acy1oxy-3-oxo-10a-steroid obtained is treated with Zinc in a solvent.

9. Process according to claim 8, wherein a A -3-oxolOu-steroid is isomerized to a A -3-0xo-l0ot-steroid by irradiation with ultraviolet light.

10. Process according to claim 8, wherein a A -3-oxo- IOOt-SltfiI'Oid selected from the group consisting of those of the androstane, pregnane, cholane, cholestane, spirostane and cardanolide series is dehydrogenated in 1,2- position by reaction with a member selected from the group consisting of 2,3-dichloro-5,6-dicyano-benzoquinone and selenium dioxide.

References Cited by the Examiner UNITED STATES PATENTS 3,001,989 9/1961 Ringold et a1 260-23955 3,198,792 10/ 1965 Reerink et a1 260-239.55

FOREIGN PATENTS 929,271 6/ 1963 Great Britain.

OTHER REFERENCES Fieser et al.: Steroids (1959), Reinhold Publishing Corp, pages 558, 559 and 572 relied on.

Schaub et al.: Chem. Ind. (London), 1961, pages 2003-4 relied on.

LEWIS GOTTS, Primary Examiner.

ELBERT L. ROBERTS, Assistant Examiner. 

1. A COMPOUND OF THE FORMULA 